Nasal Vaccine May Be the Secret Weapon Against New COVID-19 Variants

The emergence of COVID-19 variants such as delta and omicron has left scientists struggling to determine whether existing vaccinations and boosters are still effective against new strains of SARS-Cov-2.

A new response to the rapidly mutating virus may be found right at the doorstep of our lungs, says Yale’s Akiko Iwasaki, the Waldemar Von Zedtwitz professor of immunobiology. In a new study, she and her colleagues found that intranasal vaccination provides broad protection against heterologous respiratory viruses in mice, while so-called systemic immunization, which uses an injection to elicit body-wide protection, did not.

Their findings are published today (Dec. 10, 2021) in the journal Science Immunology.

“The best immune defenses are at the gate, guarding against viruses trying to get in,” said Iwasaki, senior author of the study.

Mucous membranes contain their own defense system that fights against airborne or food pathogens. When challenged, these barrier tissues produce B cells which in turn secrete immunoglobin A (IgA) antibodies. Unlike vaccines that elicit a system-wide immune response, IgA antibodies act locally on mucosal surfaces in the nose, stomach and lungs.

While the protective role of IgA-producing cells in fighting gut pathogens was well established, Iwasaki’s lab wondered whether eliciting an IgA response might also trigger a localized immune response against respiratory viruses.

In collaboration with researchers at the Icahn School of Medicine at Mount Sinai in New York, they tested a protein-based vaccine designed to trigger an IgA immune response, by administering it to mice via injections, such as usually done in systemic immunizations, and also intranasally. They then exposed mice to multiple strains of influenza viruses. They found that mice given a vaccine intranasally were much better protected against the respiratory flu than those given injections. Nasal vaccines, but not the injection, also elicited antibodies that protected the animals against various flu strains, not just the strain the vaccine was supposed to protect against.

The Yale team is currently testing nasal vaccine strains against COVID strains in animal models.

While both vaccine injections and nasal vaccines increased the levels of antibodies in the blood of mice, only the nasal vaccine enabled IgA secretion in the lungs, where respiratory viruses must lodge to infect the host, Iwasaki said.

If the nasal vaccines prove safe and effective in humans, Iwasaki envisions them being used in conjunction with current vaccines and boosters that work system-wide to add immune system reinforcement to the source of infection.

Reference: “Intranasal priming induces local lung-resident B cell populations secreting protective mucosal antiviral IgA” Dec 10, 2021, Science Immunology.
DOI: 10.1126/sciimmunol.abj5129

Other co-first authors of the study are Ji Eun Oh, Eric Song and Miyu Moriyama, all from Yale.